1. Field of the Invention
The present disclosure relates to a method for enhancing the chemical sensitivity or radiosensitivity of cancer cells by inhibiting the expression of testis-specific protein, Y-encoded-like 5 (TSPYL5).
2. Description of the Related Art
DNA methylation is one of chemical modifications that controls the expression of genetic traits, inhibits the expression of genes by reducing the reactivity of DNA and increasing the stability of DNA, and is essential for normal development. DNA methylation occurs mainly on the cytosine of CpG islands in the promoter region of a specific gene to interfere with the binding of transcription factors, thus silencing the expression of the gene. In particular, the expression of a specific gene modified by DNA hypermethylation is deeply associated with human diseases such as cancer or tumor. Thus, the promoter methylation of tumor-associated genes is an important indication of cancer, and may be used in many applications, including the diagnosis and early diagnosis of cancer, the prediction of cancer development, the prediction of prognosis of cancer, follow-up examination after treatment, and the prediction of responses to anticancer therapy.
The onset of cancer occurs through a sequence of genetic mutations. It has been found that although these genetic mutations may be accompanied by genetic changes in a DNA base sequence, epigenetic changes, which inhibit the expression of genes without being accompanied by the genetic changes in a DNA base sequence, are also important, and it has been noted that these genetic mutations are involved in the expression of various tumor-associated genes during the onset of cancer. Epigenetic changes such as promoter CpG island hypermethylation and histone modification are important mechanisms for carcinogenesis. About 60-70% of human genes have CpG islands in the promoter and some of these genes are hypermethylated to block the expression of the corresponding cancer-related gene, thus affecting tumor onset.
It has been reported that the expression of 160 or more genes is increased in the glioma cell line by inhibitors of DNA methylation and histone deacetylation. And then the TSPYL5 gene, encoding testis-specific protein, Y-encoded-like 5, is one of them, and it has been shown that the expression of the gene is significantly induced. It has been reported that the TSPYL5 gene is DNA methylated at a high frequency in a glial tumor and glioma cell line, and silenced with the CST6 gene, a metastasis suppressor and the BIK gene, an apoptosis-inducer (Kim. T. Y. et al., Cancer Res. 66(15):7490-7501, 2006). It was also confirmed that the expression of the TSPYL5 gene was often reduced in gastric cancer cell lines, 7 of 9 gastric cancer cell lines were deactivated by DNA methylation, the expression level of TSPYL5 was very low, and the promoter of the TSPYL5 gene was hypermethylated in 23 of the 36 primary gastric tumor cases. It has been also reported that the TSPYL5 gene is one of the 10 plausible genes with which Head and Neck Squamous Cell Carcinoma may be differentiated from Lung Squamous Cell Carcinoma (Anil Vachani. et al., Cancer Res. 13(10):2905-2915, 2007). However, the cellular physiological functions of the TSPYL5 gene still have not been well known.
Thus, the present inventors have performed research to understand the effects of the TSPYL5 gene on anticancer agent sensitivity and radiosensitivity, examined the expression of the TSPYL5 gene by using lung cancer cell lines, and confirmed that the expression of TSPYL5 was reduced in the H460 cell line, a cell line sensitive to radiation and anticancer agents, by DNA hypermethylation in the promoter region of the TSPYL5 gene. When the present inventors used siRNA to inhibit the expression of the TSPYL5 protein in a lung cancer cell line (A549 or H1299) based on a confirmed result that the degree of methylation was reduced in an A549 or H1299 cell line, a cell line highly resistant to radiation and anticancer agents, it was confirmed that the sensitivity to anticancer agents and radiation was significantly increased. When siRNA was used to inhibit the expression of the TSPYL5 protein in lung cancer cell line (A549 or H1299), the sensitivity to anticancer agents and radiation was significantly increased. Thus, the present inventors revealed that the use of inhibitors of expression or activity of TSPYL5 in combination with radiotherapy or chemotherapy may contribute to anticancer treatment very effectively, and made the present invention.